Energy based devices and methods for treatment of patent foramen ovale

ABSTRACT

Methods and apparatus for treatment of patent foramen ovale (PFO) provide for applying energy to tissues adjacent the PFO with a catheter device to substantially close the PFO acutely. Apparatus generally includes a catheter device having at least one energy transmission member at or near its distal end configured to apply energy to PFO tissues to acutely, substantially close the PFO. Applied energy may be monopolar or bipolar radiofrequency energy or any other suitable energy, such as laser, microwave, ultrasound, resistive heating or the like. Some embodiments of a catheter device fuirther include one or more tissue apposition members near the distal end for helping bring PFO tissues together, such as a PFO covering member, a vacuum applying member and/or the like. PFO closure via energy-based approaches of the invention may help prevent stroke, treat migraine headache, and possibly treat or prevent other medical conditions.

CROSS-REFERENCES TO RELATED APPLICATIONS

This application is a divisional of Ser. No. 11/472,630, filed on Jun.21, 2006, which is a continuation of U.S. patent application Ser. No.11/249,566, filed Oct. 12, 2005, which is a continuation of U.S. patentapplication Ser. No. 10/958,533, filed Oct. 4, 2004, which was adivisional of U.S. patent application Ser. No. 10/679,245, filed Oct. 2,2003, which claimed priority to U.S. Provisional Patent Application Nos.60/458,854, filed Mar. 27, 2003; 60/478,035, filed Jun. 11, 2003; and60/490,082, filed Jul. 24, 2003, the full disclosures of which areincorporated herein by reference. This application is related to U.S.patent application Ser. No. 10/665,974, tiled Sep. 18, 2003, the fulldisclosure of which is incorporated herein by reference.

BACKGROUND OF THE INVENTION

The invention generally relates to medical devices and methods. Morespecifically, the invention relates to energy based devices and methodsfor treatment of patent foramen ovale.

Fetal blood circulation is much different than adult circulation.Because fetal blood is oxygenated by the placenta, rather than the fetallungs, blood is generally shunted away from the lungs to the peripheraltissues through a number of vessels and foramens that remain patent(i.e., open) during fetal life and typically close shortly after birth.For example, fetal blood passes directly from the right atrium throughthe foramen ovale into the left atrium, and a portion of bloodcirculating through the pulmonary artery trunk passes through the ductusarteriosus to the aorta. This fetal circulation is shown in attachedFIG. 1.

At birth, as a newborn begins breathing, blood pressure in the leftatrium rises above the pressure in the right atrium. In most newborns, aflap of tissue closes the foramen ovale and heals together. Inapproximately 20,000 babies born each year in the US, the flap of tissueis missing, and the hole remains open as an atrial septal defect (ASD).In a much more significant percentage of the population (estimates rangefrom 5% to 20% of the entire population), the flap is present but doesnot heal together. This condition is known as a patent foramen ovale(PFO). Whenever the pressure in the right atrium rises above that in theleft atrium, blood pressure can push this patent channel open, allowingblood to flow from the right atrium to the left atrium.

Patent foramen ovale has long been considered a relatively benigncondition, since it typically has little effect on the body'scirculation. More recently, however, it has been found that asignificant number of strokes may be caused at least in part by PFO. Insome cases, stroke may occur because a PFO allows blood containing smallthrombi to flow directly from the venous circulation to the arterialcirculation and into the brain, rather than flowing to the lungs wherethe thrombi can become trapped and gradually dissolved. In other cases,thrombi might form in the patent channel of the PFO itself and becomedislodged when the pressures cause blood to flow from the right atriumto the left atrium. It has been estimated that patients with PFOs whohave already had cryptogenic strokes have a 4% risk per year of havinganother stroke.

Further research is currently being conducted into the link between PFOand stroke. At the present time, if someone with a PFO has two or morestrokes, the healthcare system in the U.S. may reimburse a surgical orother interventional procedure to definitively close the PFO. It islikely, however, that a more prophylactic approach would be warranted toclose PFOs to prevent the prospective occurrence of a stroke. The costand potential side-effects and complications of such a procedure must below, however, since the event rate due to PFOs is relatively low. Inyounger patients, for example, PFOs sometimes close by themselves overtime without any adverse health effects.

Another highly prevalent and debilitating condition—chronic migraineheadache—has also been linked with PFO. Although the exact link has notyet been explained, PFO closure has been shown to eliminate orsignificantly reduce migraine headaches in many patients. Again,prophylactic PFO closure to treat chronic migraine headaches might bewarranted if a relatively non-invasive procedure were available.

Currently available interventional therapies for PFO are generallyfairly invasive and/or have potential drawbacks. One strategy is simplyto close a PFO during open heart surgery for another purpose, such asheart valve surgery. This can typically be achieved via a simpleprocedure such as placing a stitch or two across the PFO with vascularsuture. Performing open heart surgery purely to close an asymptomaticPFO or even a very small ASD, however, would be very hard to justify.

A number of interventional devices for closing PFOs percutaneously havealso been proposed and developed. Most of these devices are the same asor similar to ASD closure devices. They are typically “clamshell” or“double umbrella” shaped devices which deploy an area of biocompatiblemetal mesh or fabric (ePTFE or Dacron, for example) on each side of theatrial septum, held together with a central axial element, to cover thePFO. This umbrella then heals into the atrial septum, with the healingresponse forming a uniform layer of tissue or “pannus” over the device.Such devices have been developed, for example, by companies such asNitinol Medical Technologies, Inc. (Boston, Mass.) and AGA Medical, Inc.(White Bear Lake, Minn.). U.S. Pat. No. 6,401,720 describes a method andapparatus for thoracoscopic intracardiac procedures which may be usedfor treatment of PFO.

Although available devices may work well in some cases, they also face anumber of challenges. Relatively frequent causes of complicationsinclude, for example, improper deployment, device embolization into thecirculation and device breakage. In some instances, a deployed devicedoes not heal into the septal wall completely, leaving an exposed tissuewhich may itself be a nidus for thrombus formation. Furthermore,currently available devices are generally complex and expensive tomanufacture, making their use for prophylactic treatment of PFOimpractical. Additionally, currently available devices typically close aPFO by placing material on either side of the tunnel of the PFO,compressing and opening the tunnel acutely, until blood clots on thedevices and causes flow to stop.

Research into methods and compositions for tissue welding has beenunderway for many years. Of particular interest are technologiesdeveloped by McNally et. al., (as shown in U.S. Pat. No. 6,391,049) andFusion Medical (as shown in U.S. Pat. Nos. 5,156,613, 5,669,934,5,824,015 and 5,931,165). These technologies all disclose energydelivery to tissue solders and patches to join tissue and formanastamoses between arteries, bowel, nerves, etc. Also of interest are anumber of patents by inventor Sinofsky, relating to laser suturing ofbiological materials (e.g., U.S. Pat. Nos. 5,725,522, 5,569,239,5,540,677 and 5,071,417). None of these disclosures, however, showmethods or apparatus suitable for positioning the tissues of the PFO forwelding or for delivering the energy to a PFO to be welded.

Causing thermal trauma to a patent ovale has been described in twopatent applications by Stambaugh et al. (PCT Publication Nos. WO99/18870 and WO 99/18871). The devices and methods described, however,cause trauma to PFO tissues to hopefully eventually cause scar tissueformation which will close the PFO. Using such devices and methods, thePFO actually remains patent immediately after the procedure and onlycloses sometime later. Therefore, a physician may not know whether thetreatment has worked until long after the treatment procedure has beenperformed. Frequently, scar tissue may fail to form or may formincompletely, resulting in a still patent PFO.

Therefore, it would be advantageous to have improved methods andapparatus for treating a PFO. Ideally, such methods and apparatus wouldhelp seal the PFO during, immediately after or soon after performing atreatment procedure. Also ideally, such devices and methods would leaveno foreign material (or very little material) in a patient's heart.Furthermore, such methods and apparatus would preferably be relativelysimple to manufacture and use, thus rendering prophylactic treatment ofPFO, such as for stroke prevention, a viable option. At least some ofthese objectives will be met by the present invention.

BRIEF SUMMARY OF THE INVENTION

The present invention generally provides devices and methods fortreating patent foramen ovale (PFO). More specifically, the devices andmethods involve advancing a catheter device to a position in the heartfor treating the patent foramen ovale and applying energy to (orremoving energy from) tissues adjacent a PFO to substantially close thePFO acutely. By “substantially,” it is meant that a stable tissue bridgewill be formed across the PFO, which will withstand physiologicpressures. A substantially closed PFO, however, may still have one ormore small gaps or openings, which will in at least some cases closeover time via the healing process. By “acutely,” it is meant that thePFO is substantially closed when the closure procedure is completed.Thus, acute closure distinguishes devices and methods of the presentinvention from prior protocols, which rely on delayed PFO closure viatissue healing and scarring. “Acutely,” for purposes of thisapplication, does not mean temporarily, since devices and methods of thepresent invention will typically provide for permanent (or at leastlong-term) PFO closure.

The phrase “tissues adjacent a PFO,” or simply “PFO tissues,” for thepurposes of this application, means any tissues in, around or in thevicinity of a PFO which may be used or manipulated to help close thePFO. For example, tissues adjacent a PFO include septum primum tissue,septum secundum tissue, atrial septal tissue lateral to the septumprimum or septum secundum, tissue within the tunnel of the PFO, tissueon the right atrial surface or the left atrial surface of the atrialseptum and the like. By “application or removal” of energy, it is meantthat energy may be transferred either to or from PFO tissues. In variousembodiments, any of a number of energy transfer devices and forms ofenergy may be used to provide such energy transfer. Types of energy usedmay include, for example, radiofrequency energy, cryogenic energy, laserenergy, ultrasound energy, resistive heat energy, microwave energy andthe like.

Application of energy to (or removal of energy from) tissues tosubstantially close the PFO acutely may sometimes be referred to as“tissue welding.” Preferably, tissue welding methods of the presentinvention will be performed without using tissue soldering material orother foreign material. In some embodiments, however, it may beadvantageous to use one or more solder materials. Various solders andother tissue soldering matrices are described more fully in U.S. patentapplication Ser. No. 10/665,974 (Attorney Docket No. 022128-000300US),which was previously incorporated by reference. Examples of tissuesolders or adhesives which may be used include, but are not limited to,autologous blood, albumin, collagen, fibrin, cyanoacrylates, musselbyssus adhesives, polymer hot melt adhesives and the like.

In some embodiments of the present invention, devices and methodsfurther provide for bringing tissues adjacent a PFO together (or“apposing” tissues). In various embodiments, tissues may be apposedbefore, during and/or after application or removal of energy to thetissues. Generally, energy application or removal will act to denaturecollagen in the PFO tissues. If the tissues are apposed before and/orduring denaturation and/or while the collagen in the tissues is allowedto renature, the collagen in once-separated tissues binds together tobring the tissues together. Therefore, although not required, someembodiments of the invention include one or more devices for bringing(and possibly holding) tissues together before, during and/or afterenergy application or removal. Such devices include, for example, PFOtissue covering members, which may also be suction or vacuum applicationmembers, expandable members within the PFO tunnel, distal tip membersfor contacting a left atrial surface of PFO tissue and the like. Byproviding for substantial, acute closure of a PFO, devices and methodsof the invention may be advantageous for preventing stroke, treatingmigraine headaches and/or preventing or treating other medicalconditions caused or exacerbated by PFO.

In one aspect of the present invention, a method of treating a PFO in aheart involves advancing a catheter device to a position in the heartfor treating the PFO and applying energy to the tissues with thecatheter device to substantially close the PFO acutely. In someembodiments, as just mentioned, the method further includes bringing thetissues at least partially together, preferably using the catheterdevice but in some embodiments using a separate device. For example, insome embodiments the tissues are brought together before applying theenergy. Optionally, the tissues may then be held together while applyingthe energy. In some embodiments, the tissues are held together after theenergy has been applied as well. The method may also involve cooling thetissues after the energy has been applied.

Bringing the tissues at least partially together may be accomplished byany of a number of suitable devices and methods. In one embodiments, forexample, the tissues are contacted with a tissue covering memberadjacent a distal end of the catheter device. The tissue covering membermay cause blood pressure in a left atrium of the heart to bring thetissues at least partially together. In some embodiments, the tissuecovering member may be further used to apply vacuum force to thetissues.

Although the catheter device may be positioned in a number of differentlocations for treating a PFO, in some embodiments advancing the catheterinvolves positioning a distal end of the catheter in a right atrium ofthe heart. Advancing the catheter may also include advancement over aguide catheter or guidewire extending into the PFO. Optionally, theguide catheter or guidewire may extend through the PFO into a leftatrium of the heart.

In some embodiments, the method further includes retracting a sheathportion of the guide catheter to expose an expanding member within thePFO, the exposed expanding member bringing the tissues adjacent the PFOat least partially together. Such an expanding member may providelateral force to the tissues adjacent the PFO, for example, and in someembodiments will do so without extending into the left atrium. As isexplained further below, such expanding members may comprise“fishmouth,” two-pronged members in one embodiment, and may beconstructed of shape memory materials, spring-loaded materials or thelike. By spreading PFO tissues laterally between two prongs (forexample), the tissues come together in the area between the prongs.Optionally, the method may also include contacting a left atrial surfaceof at least one of a septum primum and a septum secundum with a distalportion of the expanding member and retracting the expanding member tobring the tissues adjacent the PFO together. For example, the distalportion may contact the septum primum and pull it toward the right sideof the heart, into contact with the septum secundum. At some point afterthe expanding member has been used to appose the tissues adjacent thePFO, it may be advantageous to retract the expanding member to aposition within the guide catheter. For example, the expanding membermay be retracted in some embodiments before removing the guide catheterthrough the main catheter device.

As mentioned, in some embodiments the catheter device may be advancedover a guidewire rather than a guide catheter. The guidewire typicallyextends through the PFO and may include an expanding portion along itslength for expanding within the PFO. Optionally, the guidewire mayextend into the left atrium, and the method may optionally includecontacting a left atrial surface of at least one of a septum primum anda septum secundum with a distal portion of the guidewire and retractingthe guidewire to bring the tissues adjacent the PFO together.

Any suitable type of energy may be applied to the PFO tissues to provideacute PFO closure. In some embodiments, for example, monopolar orbipolar radiofrequency energy is applied, while in alternativeembodiments cryogenic, resistive heat, ultrasound, microwave, or laserenergy, heat energy in the form of heated fluid such as saline, or thelike may be applied. Energy may be applied by energizing a singleconductive member of the catheter device or multiple conductive members,in various embodiments. Generally, any suitable devices for energydelivery are contemplated.

Some embodiments of the method may further involve monitoring an amountof energy applied to the tissues. For example, monitoring the energy mayinvolve monitoring a temperature of the tissues, an impedance of thetissues and/or the like. Such a method may further involve determiningwhen a sufficient amount of energy has been applied to the tissues toacutely close the PFO. Optionally, the method may also includediscontinuing the application of energy when the sufficient amount ofenergy has been applied.

Any of the above methods may also involve directly visualizing the PFOand the adjacent tissues using at least one visualization device coupledwith the catheter device. Such a visualization device may include afiber optic device, an ultrasound device or any other suitablevisualization device.

In another aspect of the invention, a method of treating a PFO in aheart involves advancing a catheter device to a position in the heartfor treating the patent foramen ovale and removing energy from tissuesadjacent the patent foramen ovale with the catheter device tosubstantially close the patent foramen ovale acutely. Removing energyfrom the tissues may be achieved using any suitable device(s), such asby contacting the tissues with one or more cryogenic energy members. Anyof the additional or alternative method steps described above may beapplied to this aspect of the invention.

In another aspect of the invention, apparatus for treating a PFO in aheart includes a catheter device having a proximal end and a distal endand at least one energy transmission member adjacent the distal end forapplying energy to, or removing energy from, tissues adjacent a PFO toacutely close the PFO. Some embodiments further include at least onetissue apposition member adjacent the distal end for at least partiallybringing the tissues together. In some embodiments, the tissueapposition member comprises a tissue covering member. The tissuecovering member may have any suitable configuration and be constructedfrom any suitable material(s). In some embodiments, for example, thetissue covering member has a suction cup or cone shape.

In some embodiments, the tissue covering member fully covers the openingof the PFO to allow blood pressure in a left atrium of the heart tobring the tissues together. Additionally, the tissue covering member maycomprise a suction member for applying vacuum force to the tissues tobring the tissues together. Optionally, the tissue covering member maybe expandable from a first delivery dimension to a second treatmentdimension. In some embodiments, the catheter further comprises aflexible isolation portion disposed between the tissue covering memberand the catheter device to prevent unwanted movement of the tissuecovering member during use. In some embodiments, the at least one energytransmission member is coupled with the tissue covering member.

Some embodiments of the apparatus further include a guide member foradvancing through the PFO, with the catheter device being slidablydisposed over the guide member. The guide member may include, forexample a guide catheter and at least one expandable member disposedwithin the guide catheter, wherein the guide catheter is retractable toexpose the expandable member to allow it to expand within the PFO. Theexpandable member, in turn, may have any suitable configuration, but insome embodiments it includes at least two members that expand apart toprovide lateral force to the tissues adjacent the PFO, such as a“fishmouth” or two-prong expandable member. When exposed, the expandingmember may also provide dilatory force to the tissues adjacent the PFO.To provide expandability, the expandable member may be made of shapememory material, may be spring loaded, and/or the like.

In alternative embodiments, the guide member may comprise a guidewirehaving an expandable portion along its length. For example, theexpandable portion may be a divided portion, the divided portioncomprising expandable shape memory material. Optionally, the guidemember may include at least one tip for contacting a left atrial surfaceof the tissues adjacent the PFO. Such a tip may be conformable to theleft atrial surface. The guide member may be retractable to engage theat least one tip with the left atrial surface.

In any of the above embodiments, one or more guide members, or componentparts of a guide member, may act as one or more energy transmissionmembers. In some embodiments, for example, an expanding member may actas a monopolar or bipolar radiofrequency electrode.

The at least one energy transmission member of the catheter device maycomprise any suitable energy transmission device or combination ofdevices. For example, the transmission member may transmitradiofrequency energy, cryogenic energy, resistive heat energy,ultrasound energy, microwave energy, laser energy or any other form ofenergy for treating PFO tissues. In preferred embodiments, the energytransmission member comprises a monopolar or two bipolar radiofrequencytransmission members. Such a transmission member, for example, may becurved to approximate the curvature of the PFO. In other embodiments,straight transmission members, mesh or braided transmission members,multiple pin-point transmission members or the like may be used.

In some embodiments, the energy transmission member(s) are coupled withthe tissue apposition member. Thus, tissues may be brought intoapposition and energy may be applied using the tissue apposition member.In some embodiments, energy transmission member is movable along atleast part of a circumference of the at least one tissue appositionmember. In alternative embodiments, the energy transmission membercomprises a guide member for advancing through the PFO, with thecatheter device being slidably disposed over the guide member. Again,the guide member typically includes at least one expandable portion forexpanding within the PFO to at least partially bring together thetissues adjacent the PFO, and in some embodiments the expandable memberacts as the energy transmission member(s). In still other embodiments,energy transmission members may be coupled with both the tissueapposition member and the guide member/expandable member.

Apparatus of the invention may further include at least one sensorcoupled with the catheter device for sensing an amount of energydelivered to the tissues by the at least one energy transmission member.Sensors, for example, may be infrared sensors, thermistors,thermocouples or the like, though any sensors may be used. Optionally, amicroprocessor may be coupled with the at least one sensor forprocessing sensed data to determine when the amount of delivered energyhas reached a desired amount of energy.

These and other embodiments are described in further detail in thefollowing description related to the appended drawing figures.

BRIEF DESCRIPTION OF THE DRAWING FIGURES

FIG. 1 is a diagram of the fetal circulation;

FIG. 2 is a diagram of a catheter apparatus according to an embodimentof the present invention, having a conductive element and closuredevice, the catheter passing through the inferior vena cava and rightatrium and through the PFO;

FIG. 3 is a perspective view of a catheter apparatus according to anembodiment of the present invention;

FIGS. 3A and 3B are cross-sectional views of the catheter apparatus inFIG. 3;

FIG. 4 is a perspective view of a catheter apparatus according toanother embodiment of the present invention;

FIGS. 5A and 5B are perspective views of a catheter apparatus accordingto another embodiment of the present invention;

FIG. 6 is a perspective view of a catheter apparatus according toanother embodiment of the present invention;

FIG. 7 is a perspective view of a catheter apparatus according toanother embodiment of the present invention; and

FIGS. 8A-8E demonstrate a method for treating a PFO using a catheterapparatus according to an embodiment of the present invention.

FIGS. 9A-9B illustrate a catheter apparatus including a backstop andinflatable member for treating a PFO according to one embodiment of thepresent invention.

FIG. 10 illustrates a backstop device according to another embodiment ofthe present invention.

FIG. 11 illustrates a coil version of a backstop device according toanother embodiment of the present invention.

FIG. 12 illustrates a balloon version of a backstop device according toanother embodiment of the present invention.

FIG. 13A-13C illustrates a flower petal version of a backstop deviceaccording to another embodiment of the present invention.

DETAILED DESCRIPTION OF THE INVENTION

Devices and methods of the present invention generally provide forpatent foramen ovale (PFO) treatment through application or removal ofenergy. Methods involve advancing a catheter device to a position in theheart for treating the PFO and applying energy to (or removing energyfrom) tissues adjacent a PFO to substantially close the PFO acutely.Terms such as “substantially,” “acutely,” and “tissues adjacent the PFO”are defined above in the Brief Summary of the Invention. Devices of theinvention generally include a catheter device having a proximal end anda distal end and at least one energy transmission member adjacent thedistal end for applying energy to or removing energy from tissuesadjacent the PFO.

As mentioned above in the background section, FIG. 1 is a diagram of thefetal circulation. The foramen ovale is shown, with an arrowdemonstrating that blood passes from the right atrium to the left atriumin the fetus. After birth, if the foramen ovale fails to close (thusbecoming a PFO), blood may travel from the right atrium to the leftatrium or vice versa, causing increased risk of stroke, migraine andpossibly other adverse health conditions, as discussed above.

With reference to FIG. 2, one embodiment of a PFO-treatment apparatus100 may be advanced through the vasculature of a patient to a positionin the heart for treating a PFO. In this embodiment, apparatus 100includes an elongate catheter device 110 having one or more tissueapposition members 112 and one or more energy transmission members 114at or near its distal end. Optionally, catheter device 110 may beslidably disposed over a guide member 120, such as a guide catheter (asin FIG. 1), a guidewire, or the like. Guide member 120 may include, forexample, one or more expanding members 122 or other similar devices fordeploying within the PFO to help appose the adjacent tissues. In someembodiments, as described further below, expanding members 122 maycomprise (or be coupled with) one or more energy transmission members114. Generally, apparatus 100 may be used to bring together tissuessurrounding and/or adjacent the PFO and to transmit energy to thetissues to close the PFO.

Although the embodiment in FIG. 2 and many of the embodiments describedbelow include one or more tissue apposition members, devices of thepresent invention do not require such members. In some embodiments, asmentioned above and as set forth in the claims, devices may include acatheter device having one or more energy transmission members forapplying or removing energy, without any components designed forbringing the tissues together. Therefore, although much of the followingdiscussion focuses on embodiments including tissue apposition membersand the like, such members are not required.

Referring now to FIG. 3, one embodiment of a PFO-treatment apparatus 200suitably includes a catheter device 210 coupled with a tissue appositionmember 212 at its distal end. One or more energy transmission members214 may be disposed through or within catheter device 210 and/or coupledwith tissue apposition member 212. In some embodiments, catheter device210 is slidably disposed over a guide catheter 220. Guide catheter 220may contain one or more expandable elements 222, such as a guide wire orthe like. One or more radiopaque markers 224, 226 may be included oncatheter device 210, guide catheter 220 or both. Catheter device 210 mayalso include an isolation portion 228 for helping to stabilize tissueapposition member 212 during use, so that it is not caused to move dueto the flexibility of catheter device 210.

FIGS. 3A and 3B show cross-sectional views of apparatus 200 from theperspective of lines A and B in FIG. 3, respectively. In FIG. 3A,catheter device 210 is shown, having a guide catheter lumen 232, twoenergy transmission member lumens 234 and a vacuum lumen 236. As shownin FIG. 3B, guide catheter 220 includes an expandable element lumen 238.Guide catheter lumen 232 may sometimes be configured with an innerdiameter (or “profile”) that is shaped (or “keyed”) to allow guidecatheter 220 to pass easily through lumen 232. This feature isdemonstrated in FIGS. 3A and 3B, where guide catheter 220 and guidecatheter lumen 232 each have an ovoid shape.

In general, catheter device 210 comprises an elongate, flexible catheterwhich may be advanced through the vasculature of a patient to a positionin the heart for treating a PFO. Thus, catheter device 210 may have anysuitable length, diameter, cross-sectional profile and the like, and maybe constructed of any suitable material. Tissue apposition member 212(or multiple tissue apposition members in some embodiments) is disposedat or near the distal end of catheter device 210. Although manydifferent types of devices may be used to bring tissues of the PFOtogether, in one embodiment (shown in FIG. 2) tissue apposition member212 comprises a PFO-covering member. PFO-covering tissue appositionmember 212 may be positioned to contact adjacent PFO tissues to fullycover, or block, the opening of the PFO. This blocking of the PFO mayprevent right-to-left shunting of blood and may allow blood pressure inthe left atrium to bring the septum primum and septum secundum at leastpartially together to close the PFO. Therefore, simply by forming a sealor blockage over the PFO, tissue apposition member 212 may help bringthe PFO tissues together to assist in PFO closure.

In this and other embodiments, tissue apposition member 212 may alsoinclude one or more vacuum members for applying vacuum to the PFOtissues. In one embodiment, for example, suction lumen 236 (FIG. 3A) mayextend from the proximal end to the distal end of catheter device 210,opening into one or more vacuum-application apertures at the distal endof tissue apposition member 212. The vacuum-application aperture(s) mayhave any suitable configuration, such as a continuous apertureencircling tissue apposition member 212, multiple apertures encirclingtissue apposition member 212 or in any other suitable configuration ator near its distal end, or the like. In still another embodiment, vacuummay be applied via a large, central lumen in tissue apposition member212. In any case, vacuum force may be used to bring PFO tissues togetherand/or to secure tissue apposition member 212 and thus catheter device210 to the PFO tissues.

Tissue apposition member 212, especially when configured as aPFO-covering member, may be collapsible/expandable to facilitateadvancement and delivery of catheter device 210. For example, tissueapposition member 212 may comprise a collapsible polymeric coverdisposed over an expandable/collapsible frame. In other embodiments,tissue apposition member 212 may be constructed of a shape memorymaterial, such as nitinol or another shape memory metal, springstainless steel or the like, to allow catheter device 210 to bedelivered through vasculature and then allow tissue apposition member212 to expand to contact and appose the PFO tissues. In someembodiments, catheter device 210 and tissue apposition member 212 may bedelivered to a location for PFO treatment through an introducer sheath.To further enhance the use of apparatus 200, an angle between catheterdevice 210 and tissue apposition member 212 may be selected toapproximate a convenient angle for delivery and/or deployment. In oneembodiment, for example, the angle between catheter device 210 andtissue apposition member 212 may approximate the angle between theinferior vena cava and the interatrial septum. Any other configuration,combination of angles and the like is contemplated, however. In someembodiments, for example, direct steering of the angle of tissueapposition member 212 relative to catheter device 210 may be employed toenhance delivery of catheter device 210 to a treatment site.

To further facilitate use of apparatus 200, catheter device 210 mayinclude one or more radiopaque markers 226 for facilitatingvisualization of the device 210. Catheter device 210 may also include a“flexible isolation portion” 228, which in some embodiments comprises arigid but shapeable portion disposed toward the distal end of catheterdevice 210, between tissue apposition member 212 and the generallyflexible proximal portion of catheter device 210. Flexible isolationportion 228 may help to isolate tissue apposition member 212 from someor all movement experienced by the more flexible, proximal portion ofcatheter device 210, thus allowing a PFO treatment procedure to beperformed without significant movement of tissue apposition member 212.In other embodiments, flexible isolation portion 228 may be moreflexible than the more proximal portion of catheter device 210, thusenhancing maneuverability, shapability or the like of the position oftissue apposition member 212 relative to the more proximal portion.

Energy transmission members 214 may comprise any of a number of devicesand may transmit any suitable type of energy for closing a PFO. Sometypes of energy which may be used, for example, include radiofrequency,cryogenic, resistive heat, ultrasound, microwave and laser energy.Radiofrequency energy transmission members 214 may be either monopolaror bipolar, with monopolar catheter devices also including a groundingmember. Energy transmission members 214 may have any suitableconfiguration. For example, they may have a curved shape to approximatea radius of curvature of the PFO, as shown in FIG. 3, or they may beconfigured as points for spot-welding the PFO tissues, as a circularmember for welding around the circumference of PFO tissues, as one ormore mesh or braided members disposed within the orifice of tissueapposition member 212 or the like. In some embodiments, energytransmission members 214 are fixedly coupled with tissue appositionmember 212, while in other embodiments energy transmission members 214are movable within tissue apposition member, for example to move aboutthe circumference of the PFO to weld PFO tissues at multiple locations.

As mentioned earlier, the phrase “tissue welding” herein is used to meanapplication of energy to (or removal of energy from) PFO tissues tosubstantially and acutely close the PFO. Energy transmission members 214generally provide for transfer of energy to or from PFO tissues todenature collagen in the tissues, and when the collagen is allowed torenature, with the tissues apposed, the once separated tissues bindtogether to form a stable tissue bridge. This stable tissue bridgesubstantially and acutely closes the PFO, preferably permanently. PFOtissues may, in some embodiments, be brought and held together by one ormore tissue apposition members 212. Energy transmission members 214provide sufficient energy transfer, for a sufficient time, to weld thetissues. The time span of energy transmission may be, for example, fromabout 0.5 seconds to about 15 minutes, and more preferably from about 30seconds to about 5 minutes. Energy transmission, in some embodiments,may be from about 0.5 Watts to about 100 Watts, and more preferably fromabout 2 Watts to about 20 Watts. Any other suitable energy and timingcombination may also be used. In one experimental example, a PFO in asection of pig heart tissue used ex-vivo in a flowing saline testfixture was closed by applying suction to appose the PFO tissues andapplying RF energy at approximately 25 watts for 7 minutes. RF energyapplication was then discontinued, but suction was continued for anadditional 1 minute to keep tissues in apposition while the tissuecooled, to allow collagen in the tissues to reorganize and bind togetherto form a stable tissue bridge. Many other energy amounts, energyapplication times, tissue apposition times and the like arecontemplated, however.

Although any type of energy may be transmitted by energy transmissionmembers 214, some embodiments will make use of monopolar or bipolarradiofrequency

(RF) energy. Devices may use monopolar radiofrequency energy, forexample, wherein energy is applied simultaneously to all conductiveelements, completing the circuit through an external ground pad affixedto the skin of the patient. Alternatively, bipolar energy may be appliedto all conductive elements simultaneously, and the circuit completedthrough a ground element incorporated elsewhere on apparatus 200.Further embodiments may include applying bipolar energy between two ormore energy transmission members 214, which are electrically isolatedfrom one another within catheter device 210.

Control systems coupled with energy transmission members 214 or tissueapposition member 212, or otherwise disposed within apparatus 200, maysense an amount of energy delivered to PFO tissues and, optionally, mayautomatically stop energy delivery upon detecting a change in conditionof energy delivery, for instance an increase in electrical resistance orimpedance in PFO tissues or in apparatus 200, an increased energy drawfrom the treatment apparatus, and/or the like. In some embodiments,energy delivery may be automatically stopped when an amount of deliveredenergy reaches a desired level, such as an amount of energy sufficientto substantially close the PFO. The amount of delivered energy may bemonitored by any suitable method, such as monitoring temperature orimpedance in PFO tissues or the like. In some embodiments, one or moresensors coupled with tissue apposition member 212, energy transmissionmembers 214, or any other part of apparatus 200 may be used formonitoring such indicia. Examples of sensor devices include but are notlimited to infrared sensing devices, thermistors and thermocouples. Acontrol system may also include a microprocessor coupled with thesensors to determine when a desired amount of energy has been deliveredand/or to automatically stop energy transmission. In alternativeembodiments, a microprocessor may be included in apparatus 200 which cansense, monitor and control energy delivery, thus not requiring separatesensors.

With continued reference to FIG. 3, some embodiments of apparatus 200include guide catheter 220, or an alternative guide member as discussedfurther below. Guide catheter 220 is generally a flexible catheter alongwhich catheter device 210 may be slidably advanced to a position for PFOtreatment. Guide catheter 210 is configured to fit at least partiallywithin a PFO and optionally through a PFO into the left atrium of theheart. Optionally, one or more radiopaque markers 224 may be included onguide catheter.

Guide catheter 220 may contain one or more expandable members 222 orother similar devices for expanding within the PFO to help bring the PFOtissues together, anchor catheter device to the PFO tissues, or both. Asshown in FIG. 3, for example, a “fish mouth” or two-prong expandablemember 222 may be deployed within a PFO. When the two arms of the fishmouth separate, PFO-adjacent tissues are stretched laterally such thatthey tend to come together in the middle. In some embodiments,expandable members 222 may assist in PFO tissue apposition either whileextending into the left atrium, while in other embodiments expandablemembers 22 do not extend into the left atrium.

Expandable member 222 may have any suitable configuration and may beconstructed from any suitable materials. For example, expandable member222 may be spring loaded, made of shape memory material, such as nitinolor spring stainless steel or the like. Alternatively, expandable member222 may be expanded mechanically by one or more expansion memberscoupled with expandable member 222 and controlled via an actuator at theproximal end of guide catheter 220. During delivery of guide catheter220, expandable member 222 reside within guide catheter 220. Guidecatheter 220 may then be withdrawn to deploy expandable member 222either within the PFO or within the left atrium to be drawn back intothe PFO. In some embodiments, expandable member 222 has one or morepre-shaped or shapeable distal tips 223. Tips 223 may be used, forexample, to help locate and cross the PFO. Tips 223 may also be used tocontact a left atrial surface of the septum primum or other PFO tissue,so that when the expandable member 222 is pulled proximally tips 223help bring the PFO tissues together and/or anchor apparatus 200.

In some embodiments, one or more expandable members 222 may include orbe coupled with one or more energy transmission members. For example,expandable member 222 may include one or more radiofrequencytransmission members for monopolar or bipolar RF transmission. A fishmouth expandable member 222, for example, may include a bipolar RFtransmission member on each prong of the fish mouth. In someembodiments, energy transmission members may be included in or coupledwith both expandable member 222 and tissue apposition member 212. In anysuch embodiments, some portions of the energy transmission member(s) maybe insulated, to prevent unwanted energy transmission to tissues. Forexample, in some embodiments a distal tip extending to contact a leftatrial surface of PFO tissues may be insulated to prevent energytransmission from the tip.

Referring now to FIG. 4, an alternative embodiment of a PFO-treatmentapparatus 300 suitably includes a catheter device 310 having a tissueapposition member 312, radiopaque marker 326 and flexible isolationportion 328. For exemplary purposes only, this embodiment is shownhaving one energy transmission member 314, such as a monopolar RFtransmission member. As shown, apparatus 300 may also include aguidewire 320, over which catheter device 310 may be advanced. Guidewire320 includes a split, expandable portion 322, which may be released fromcatheter device 310 to expand within a PFO to bring PFO tissuestogether. Guidewire 320 also suitably includes a distal tip 323 forlocating and crossing a PFO and/or for contacting a left atrial surfaceof the septum primum or other PFO tissue.

Apparatus 300 of FIG. 4 may include any of the features described abovein relation to FIG. 3. In the embodiment in FIG. 4, apparatus 300 doesnot include a guide catheter, but instead includes guidewire 320.Guidewire 320 may serve many or all of the functions of the guidecatheter and expanding member described above in reference to FIG. 3.Split portion 322 of guidewire 320 may be constructed of shape memorymaterial or other suitable materials to allow it to expand when releasedfrom catheter device 310. Additionally, split portion 322 may include orbe coupled with one or more energy transmission members instead of or inaddition for energy transmission member(s) 314 coupled with tissueapposition member 312. Guidewire 320 may also include one or more distaltips 323, which again may be used to locate and cross a PFO and/or tohelp appose PFO tissues. In some embodiments, tip 323 may also includeor be coupled with one or more energy transmission members.

Referring now to FIGS. 5A and 5B, another embodiment of a PFO-treatmentapparatus 400 suitably includes a catheter device 410 having a tissueapposition member 412, radiopaque markers 426 and flexible isolationportion 428. As shown, apparatus 400 may also include a guidewire 420,over which catheter device 410 may be advanced. Guidewire 420 includes asplit, expandable portion 422, which may be released from catheterdevice 410 to expand within a PFO to bring PFO tissues together.Guidewire 420 also suitably includes a distal tip 423 for helping locateand cross the PFO and/or for contacting a left atrial surface of theseptum primum or other PFO tissue to help bring the PFO tissuestogether. In this embodiment, catheter device 410 also includes abraided portion 430 which includes the proximally-disposed tissueapposition member 412 and a more distal energy transmission portion 432,the latter of which is coupled with energy transmission members 414.Tissue apposition member 412 and energy transmission portion 432 may bea unitary braided member, with tissue apposition member 412 configuredto cover energy transmission portion 432 in a retracted position and toprovide vacuum force application.

In use, catheter device 410 is typically advanced over guidewire 420 toa treatment location. Split portion 422 and optionally distal tip 423are then used to help appose the tissues adjacent the PFO. Before,during or after retraction of guidewire 420, energy transmission portion432 is retracted into tissue apposition member 412. PFO tissue is thenbrought together using tissue apposition member 412, and energy istransmitted to the tissues using energy transmission portion 432. Insome embodiments, tissue apposition member 412 provides for applicationof vacuum energy to the tissues to suction the tissues at leastpartially into tissue apposition member 412, thus enhancing contact ofthe tissues with energy transmission portion 432. Energy transmissionportion 432 may comprise, for example an electrode mesh material, whiletissue apposition member 412 may comprise an elastic coated mesh orother material. Again, any features described above in reference toother embodiments may be applied to the embodiment shown in FIGS. 5A and5B.

With reference now to FIG. 6, another embodiment of a PFO-treatmentapparatus 500 suitably includes a catheter device 510 having a tissueapposition member 512, energy transmission members 514, radiopaquemarker 526 and flexible isolation portion 528. For simplicity, apparatus500 is shown without a guide catheter or guidewire, though either may beincluded. In this embodiment, tissue apposition member 512 includes ribsor “bellows” 540 to facilitate placement and/or alignment of tissueapposition member 512 relative to the septal wall tissues to be treatedand/or to enhance adherence of apparatus 500 to the septal wall. Forexample, ribs 540 may allow catheter device 510 to move relativelyfreely relative to tissue apposition member 512, without displacingtissue apposition member 512 from the PFO tissues.

Referring now to FIG. 7, another embodiment of a PFO-treatment apparatus600 suitably includes a catheter device 610 having a tissue appositionmember 612, energy transmission members 614, radiopaque marker 626 andflexible isolation portion 628. Apparatus 600 is shown without a guidecatheter or guidewire, though either may be included. In thisembodiment, tissue apposition member 612 includes multiple struts 650covered by a covering 652, which may comprise a polymeric covering orany other suitable material. Struts 650 may be self-expanding or mayopen via a mechanical opening actuator coupled with struts 650, such asopening apparatus used to open an umbrella. Energy transmission members614 are coupled with self-expanding struts 650 on the internal surfaceof tissue apposition member 612, so as to contact PFO tissue that ispulled within tissue apposition member 612, such as by applied vacuumforce and/or by blood pressure from the left atrium.

FIGS. 8A-8E demonstrate a method for treating a PFO according to oneembodiment of the present invention. It should be emphasized that thisis merely one possible embodiment, and that many alternative methods arecontemplated. For example, steps may be modified, repeated, added ordeleted from the method, the order of steps may be changed, and/or thelike, without departing from the scope of the invention as defined bythe appended claims. Therefore, the foregoing description should not beinterpreted to limit the scope of the invention in any way.

That being said, in one embodiment, a PFO treatment method includesadvancing a guide catheter 720 through the PFO, between tissues Tadjacent the PFO, the guide catheter 720 containing an expandable member(FIG. 8A). Guide catheter 720 is then retracted (proximally pointingarrow) to expose expanding member 722 (FIG. 8B). Expanding member 722may be exposed/expanded within the PFO, or may alternatively beexposed/expanded within the left atrium and pulled back into the tunnelof the PFO. Expanding member 722 may also include one or more distaltips 723, which may help to locate the PFO, cross the PFO, appose thetissues T and/or to anchor guide catheter 720 to the tissues T.

Once guide catheter 720 is in place and expandable member 722 isdeployed, catheter device 710 may be advanced over guide catheter 720 toa position for treatment of the PFO (FIG. 8C). Catheter device 710typically includes a tissue apposition member 712 (shown here incross-section for clarity) and one or more energy transmission members714. Suction may be applied using tissue apposition member 712, leftatrial pressure may be used, or both, to bring tissues T adjacent thePFO together (FIG. 8D). Once tissue apposition member 712 is placedand/or activated, guide catheter 720 and expandable member 722 may beremoved through catheter device 710, leaving the tissues T apposed andcatheter device in place, as in FIG. 8D. Alternatively, guide catheter720 and expandable member 722 may be left in place during a firstwelding to close the majority of the PFO and then removed. The smallpatent portions of the PFO remaining after the guide catheter 720 andexpandable member 722 are removed may then be closed by a second weld ormay be left open and allowed to close via healing or scarring. Tissueapposition member 712 may be used to hold tissues T together before,during and/or after energy transmission members 714 weld the tissues Ttogether. Such holding of the tissues together and application of energyto weld the tissues may be performed for any suitable time, such as forless than one second to many minutes. Once a sufficient amount of energyhas been applied to the tissues T to acutely close the PFO, catheterdevice 710 is removed, leaving a closed PFO, as in FIG. 8E.

Apparatus and methods according to the present invention may rely onenergy, in various forms, to seal the PFO, either with or without anassociated implant device. As an alternative to implant-based devices,systems according to the present invention can function to weld the PFOclosed with no implant left behind. As illustrated in FIGS. 9A and 9B,in some embodiments, a backstop and energy delivery catheter are placedin contact with the PFO, and energy is delivered to disrupt the collagenmatrix of the primum and secundum to cause fusion of the two parts ofthe PFO. Energy used can be monopolar or biopolar RF (in which case thebackstop acts as energy return), ultrasound, laser, microwave, orresistance heating. Protein solder may be introduced to facilitate theweld.

Referring to FIG. 9A, one embodiment of a backstop catheter device 800for treating a PFO may include an outer catheter element 802, an innercatheter element 804, a backstop 806 coupled with a member 808 extendingthrough the inner shaft 804, and energy delivery arms 810. Energydelivery arms 810 can include ultrasound transducers, microwaveantennae, or RF electrodes. The backstop catheter device 800 is advancedthrough the PFO and used to help advance an energy delivery catheter tothe right atrial side of the PFO. Relative translation of an inner 804and outer catheter element 802 deploy a set of arms 810 which carry theenergy delivery elements. The energy delivered breaks down the collagenin each part of the PFO, and allows the tissues to be welded together.The energy delivered could take the form of RF, microwave, orultrasound. RF energy can either be monopolar, in which the backstop 806is electrically insulated such that it is not part of the energydelivery path, or bipolar, in which case the backstop 806 acts as theenergy return electrode. If desired, the inner catheter 804 of thedevice 800 can be used to infuse liquid albumin to act as a proteinsolder for the system. Alternatively, the shaft of the backstop 806could be covered with a tube of solid or braided material made of, orsoaked in, a tissue solder. After delivery of the energy and activationand bonding of the tissue solder to the PFO walls, the backstop 806 iswithdrawn through the PFO and the entire system is withdrawn.

As illustrated in FIG. 9B, in another embodiment, a catheter device 820can include an expandable balloon member 822 and an expandable backstop824. The balloon catheter 820 can be outfitted with sections 826 ofpiezo film/foil which can be driven electrically to produce anultrasound signal to heat and seal a PFO. The balloon member 822 andexpandable backstop 824 are used to position the catheter device 820 inthe desired location and energy is then applied via the piezo film/foil826 for treating the PFO.

Variations of a backstop device according to the present invention areillustrated in FIGS. 10 through 13. Referring to FIG. 10, a backstopdevice 830 can have an inferior bias to preferentially engage the primumwithout interfering with the left atrial wall. Embodiments of thebackstop device 830 are shown including prongs 832 and wire loops 834.

Referring to FIG. 11, a backstop device can include a coiled version840, where a guidewire reforms into a coil 842 when introduced into theleft atrium. The coil can be reverse-bias coil, so traction causes aformer seat, or inferior-bias coil 846, so there is less contact withthe left atrial wall superiorly. A flat coil version 848 of a backstopdevice is also shown.

FIG. 12 shows a balloon version backstop device, with a soft,low-pressure balloon 852 and a fixed wire 854. The balloon 854 can beconcentric to the shaft 856, or inferior-biased for clearance. Theinferior-bias balloon 858 preferentially engages the primum withouthitting the left atrial wall. The device can be fixed-wire,over-the-wire, or tip-mounted with no central lumen for a guide wire orfor inflation only.

FIGS. 13A through 13C show a backstop device 860 with a normally-openflower petal 862, where nitinol petals 862 are biased open, and attachedproximal to an outer catheter 864, distal to a core wire 866.Translation of the core wire 866 opens and closes the petals 862. Thepetals 862 are shown attached to the core wire 866 and the outercatheter 864 (FIG. 13B). The core wire 866 is advanced to collapse thepetals 862 (FIG. 13C).

As mentioned above, the foregoing method may be altered in any number ofways without departing from the scope of the invention. In someembodiments, for example, tissues adjacent the PFO are brought at leastpartially together and energy is applied to the tissues to acutely closethe PFO with fewer steps and/or fewer device components than justdescribed. For example, application of suction to appose tissues is notrequired in all embodiments. Furthermore, a variety of different typesof energy may be applied to the tissues from a variety of differentlyconfigured energy transmission devices. In some embodiments, one or moreof the steps described above may be repeated one or more times, such asby repeating a tissue welding step. The above description, therefore, isprovided for exemplary purposes only.

Although the foregoing description is complete and accurate, it hasdescribed only exemplary embodiments of the invention. Various changes,additions, deletions and the like may be made to one or more embodimentsof the invention without departing from the scope of the invention.Additionally, different elements of the invention could be combined toachieve any of the effects described above. Thus, the description aboveis provided for exemplary purposes only and should not be interpreted tolimit the scope of the invention as set forth in the following claims.

1. An apparatus for treating a patent foramen ovale (PFO) in a heart of a patient, comprising: a guidewire for advancing through tissues of the PFO; a catheter device slidably disposed over the guidewire, the catheter device having a proximal end and a distal end; and at least one energy transmission member adjacent to the distal end for applying energy to or removing energy from tissues adjacent to the PFO to substantially close the PFO.
 2. The apparatus of claim 1, wherein the guidewire comprises a distal tip for locating and extending through the PFO.
 3. The apparatus of claim 1, wherein the guidewire comprises at least one energy transmission member.
 4. The apparatus of claim 1, wherein the guidewire comprises an expandable portion for expanding on the left atrial side of the heart as to at least partially bring the tissues together.
 5. The apparatus of claim 4, wherein the expandable portion comprises an expandable backstop.
 6. The apparatus of claim 1, wherein the guidewire comprises an expandable member for expanding within the PFO to at least partially bring together the tissues adjacent to the PFO.
 7. The apparatus of claim 6, wherein the expandable member comprises at least one energy transmission member.
 8. The apparatus of claim 1, wherein the at least one energy transmission member transmits at least one of radiofrequency energy, cryogenic energy, heat energy, ultrasound energy, microwave energy and laser energy.
 9. The apparatus of claim 8, wherein the at least one energy transmission member comprises at least one monopolar radiofrequency transmission member.
 10. The apparatus of claim 8, wherein the at least one energy transmission member comprises at least two bipolar radiofrequency transmission members. 